Issue 29, 2018

Tuning the affinity of catechols and salicylic acids towards Al(iii): characterization of Al–chelator interactions

Abstract

Due to aluminum's controversial role in neurotoxicity, the goal of chelation therapy, the removal of the toxic metal ion or attenuation of its toxicity by transforming it into less toxic compounds, has attracted considerable interest in the past years. In the present paper we present, validate and apply a state-of-the-art theoretical protocol suitable for the characterization of the interactions between a chelating agent and Al(III). In particular, we employ a cluster-continuum approach based on Density Functional Theory calculations to evaluate the binding affinity of aluminum for a set of two important families of aromatic chelators: salicylic acids and catechols. Our protocol shows very good qualitative agreement between the computed binding affinities and available experimental stability constants (log β) values for 1 : 1, 1 : 2 and 1 : 3 complexes. Then, we have investigated the nature of the Al–O bond in an enlarged dataset of 27 complexes of 1 : 1 stoichiometry, by means of the QTAIM and Energy Decomposition Analysis (EDA). Quite interestingly, we have found that although the Al–O interaction is mainly electrostatic, there is a small but significant degree of covalency that explains the modulation of binding affinities in both families of compounds by the addition of electron donating (CH3, OCH3) or withdrawing (NO2, CF3) substituents. The role of aromaticity and the mechanisms of action of the different functional groups were also evaluated. Finally, we have analyzed the competition between Al(III) and proton toward the binding of these chelators, giving a rationalization of the different trends found experimentally between log β and the amount of free aluminum in solution in the presence of a given ligand (p[Al]). In summary, we propose a validated and comprehensive computational protocol that can provide a valuable help toward the design and tuning of new efficient aluminum chelators.

Graphical abstract: Tuning the affinity of catechols and salicylic acids towards Al(iii): characterization of Al–chelator interactions

Supplementary files

Article information

Article type
Paper
Submitted
06 Apr 2018
Accepted
16 May 2018
First published
11 Jun 2018
This article is Open Access
Creative Commons BY-NC license

Dalton Trans., 2018,47, 9592-9607

Tuning the affinity of catechols and salicylic acids towards Al(III): characterization of Al–chelator interactions

G. Dalla Torre, J. I. Mujika, E. Formoso, E. Matito, M. J. Ramos and X. Lopez, Dalton Trans., 2018, 47, 9592 DOI: 10.1039/C8DT01341A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements